Appetitive processes (e.g., reward-seeking and some aspects of craving) represent only one side of addiction; failed attempts to exert "self-control" over one's drug use are built-in to the clinical diagnosis of substance dependence. Attempts to study brain substrates of self-control have generally relied on laboratory models, such as decision-making tasks (e.g., the Iowa Gambling Task) and speeded tests of inhibitory control (e.g., the Go/No-Go Task) that have uncertain relevance to abstaining from drug use. We propose to identify substrates of self-control more directly using functional Magnetic Resonance Imaging (fMRI) in conjunction with a specialized apparatus that allows cigarette smoke inhalation in the scanning environment. Fifty cigarette smokers (abstinent 12 h) will complete a "Smoking Self-Control Challenge" that has been developed through successful pilot work. The task includes two types of 20-sec trials: "Smoke Unavailable" trials in which participants are signaled that a valve allowing cigarette smoke inhalation is closed, and "Smoke Available" trials, in which smoke is immediately available, but participants are encouraged to "try not to smoke on as many of these rounds as you can manage". The primary functional measure will be the difference in fMRI signal between Smoke Available trials in which the participant abstains, and trials in which smoke was not available ("Voluntary Abstinence" - "Smoke Unavailable"). Craving will be measured on every trial (by button presses) to allow for its covariation, as well as to allow assessment of its potential moderating effect on neural activity during voluntary abstinence. The fMRI task will be given during two sessions separated by approximately two weeks. Based on preliminary data, we anticipate that voluntary abstinence will be associated with increased neural activity in the right ventrolateral and dorsolateral prefrontal cortex as well as in the dorsal anterior cingulate cortex and supplementary motor area. Standard psychometric techniques will be applied to assess the reliability and short-term stability of performance and of fMRI signal change during the task. Two additional days of behavioral testing will allow performance on the task to be related to established measures of decision-making, inhibitory control, and personality. The proposed method will allow imaging studies of neural systems underlying self-control, complimenting existing imaging methods used to study craving for cigarettes and drugs of abuse. With the primary procedures already operational and in use, this 2-year project should yield valuable insights into the substrates of self-control, with both basic science and clinical implications. [unreadable] [unreadable] [unreadable]